The objectives of the proposed research are to investigate the rheological behavior of normal and abnormal red cell membranes (RCM), to study the interactions of RCM with the environment, and to correlate these functions with the molecular organization of RCM, both in health and in hematological diseases. Rheology of normal and abnormal RCM during deformation at constant area and during area stretching (including hemolysis) will be studied on intact red cells (Proj. A) and on monolayers prepared from RCM components (Proj. B), and will be modeled by theoretical computatton (Proj. C). The rheological data will be correlated with RCM structure determined by ultrastructural and cytochemical methods (Core). A similar correlative approach will be used in studies on ultrastructural and rheological changes of red cells in pregnancy (Proj. D) and alterations of sickle cell membrane during cyclic deoxygenation-oxygenation (Proj. E). The mechanism of membrane transport of hexoses will be studied in RBC ghosts (Proj. F) and RCM monolayers (Proj. G), and the transport process will be correlated with the molecular organization of RCM (exoface, RCM interior and endoface) determined by cytochemical methods (Proj. F). The expression of i-I antigens on the exoface of sickle cell membrane will be correlated with the cell content of HbF (Proj. E). The forces involved in the interaction of the RCM exoface with macromolecules (including abnormal plasma proteins) will be studied experimentally (Proj. H) and the micromechanics of cell aggregation will be modeled theoretically (Proj. C). The ultimate aim of the research is to provide the fundamental knowledge needed for improving diagnosis and treatment of hematological diseases.